Monounsaturated fat-rich diet reduces body adiposity in women with obesity, but does not influence energy expenditure and substrate oxidation: a parallel randomized controlled clinical trial.

BACKGROUND: Obesity is an important and growing health problem whose treatment involves dietary changes. In this context, studying the role of macronutrients in weight loss is required in order to understand which strategies may be applied for weight loss. We aimed to evaluate the effects of diets rich in polyunsaturated (PUFAs) and monounsaturated fatty acids (MUFAs) on resting energy expenditure (REE), substrate oxidation, and weight loss in women with obesity. METHODS: Randomized, controlled, single blind, parallel-group clinical trial was conducted for 60 days. Participants (n = 32) were divided into three groups: G1= normocaloric PUFAs-rich diet (12% of total energy expenditure (TEE), 10% of n-6 and up to 2% of n-3); G2= normocaloric MUFAs-rich diet (15-20% TEE); and G3= maintenance of the usual diet. Anthropometric and metabolic variables (REE and substrate oxidation by indirect calorimetry) were evaluated. RESULTS: G2 decreased body weight (-1.92 ± 1.99 kg, P = 0.02), body mass index (BMI) (-0.69 ± 0.70 kg/m2; P = 0.02), waist circumference (WC) (-1.91 ± 1.82 cm; P = 0.02), and body fat (-1.14 ± 1.53 kg; P = 0.04). CONCLUSION: MUFAs-rich diet reduces body weight, BMI, body fat, and WC. CLINICAL TRIALS: NCT02656940. CLINICAL TRIAL REGISTRATION: Clinical Trials: NCT02656940.

Protective effect of Chromobacterium violaceum and violacein against bone resorption by periodontitis.

OBJECTIVES: The aim of this study was to evaluate the potential protective effect of Chromobacterium violaceum and violacein against periodontitis, in experimental models. MATERIALS AND METHODS: A double-blind experimental study on the exposure to C. violaceum or violacein in experimentally ligature-induced periodontitis, as preventive factors against alveolar bone loss by periodontitis. Bone resorption was assessed by morphometry. Antibacterial potential of violacein was assessed in an in vitro assay. Its cytotoxicity and genotoxicity were evaluated using the Ames test and SOS Chromotest assay, respectively. RESULTS: The potential of C. violaceum to prevent/limit bone resorption by periodontitis was confirmed. Daily exposure to 106 cells/ml in water intake since birth and only during the first 30 days of life significantly reduced bone loss from periodontitis in teeth with ligature. Violacein extracted from C. violaceum was efficient in inhibiting or limiting bone resorption and had a bactericidal effect against Porphyromonas gingivalis in the in vitro assay. CONCLUSIONS: We conclude that C. violaceum and violacein have the potential to prevent or limit the progression of periodontal diseases, in an experimental model. CLINICAL RELEVANCE: The effect of an environmental microorganism with potential action against bone loss in animal models with ligature-induced periodontitis represents the possibility of understanding the etiopathogenesis of periodontal diseases in populations exposed to C. violaceum and the possibility of new probiotics and antimicrobials. This would imply new preventive and therapeutic possibilities.

Ouabain Effects on Human Anaplastic Thyroid Carcinoma 8505C Cells.

Anaplastic thyroid carcinoma (ATC) is a rare, but aggressive, carcinoma derived from follicular cells. While conventional treatments may improve patients' survival, the lethality remains high. Therefore, there is an urgent need for more effective ATC treatments. Cardiotonic steroids, such as ouabain, have been shown to have therapeutic potential in cancer treatment. Thus, we aimed to evaluate ouabain's effects in human anaplastic thyroid cells. For this, 8505C cells were cultured in the presence or absence of ouabain. Viability, cell death, cell cycle, colony formation and migratory ability were evaluated in ouabain-treated and control 8505C cells. The expression of differentiation and epithelial-to-mesenchymal transition (EMT) markers, as well as IL-6, TGFb1 and their respective receptors were also quantified in these same cells. Our results showed that ouabain in vitro decreased the number of viable 8505C cells, possibly due to an inhibition of proliferation. A reduction in migration was also observed in ouabain-treated 8505C cells. In contrast, decreased mRNA levels of PAX8 and TTF1 differentiation markers and increased levels of the N-cadherin EMT marker, as well as IL-6 and TGFb1, were found in ouabain-treated 8505C cells. In short, ouabain may have anti-proliferative and anti-migratory effect on 8505C cells, but maintains an aggressive and undifferentiated profile.

Exercise Improves Redox Homeostasis and Mitochondrial Function in White Adipose Tissue.

Exercise has beneficial effects on energy balance and also improves metabolic health independently of weight loss. Adipose tissue function is a critical denominator of a healthy metabolism but the adaptation of adipocytes in response to exercise is insufficiently well understood. We have previously shown that one aerobic exercise session was associated with increased expression of antioxidant and cytoprotective genes in white adipose tissue (WAT). In the present study, we evaluate the chronic effects of physical exercise on WAT redox homeostasis and mitochondrial function. Adult male Wistar rats were separated into two groups: a control group that did not exercise and a group that performed running exercise sessions on a treadmill for 30 min, 5 days per week for 9 weeks. Reactive oxygen species (ROS) generation, antioxidant enzyme activities, mitochondrial function, markers of oxidative stress and inflammation, and proteins related to DNA damage response were analyzed. In WAT from the exercise group, we found higher mitochondrial respiration in states I, II, and III of Complex I and Complex II, followed by an increase in ATP production, and the ROS/ATP ratio when compared to tissues from control rats. Regarding redox homeostasis, NADPH oxidase activity, protein carbonylation, and lipid peroxidation levels were lower in WAT from the exercise group when compared to control tissues. Moreover, antioxidant enzymatic activity, reduced glutathione/oxidized glutathione ratio, and total nuclear factor erythroid-2, like-2 (NFE2L2/NRF2) protein levels were higher in the exercise group compared to control. Finally, we found that exercise reduced the phosphorylation levels of H2AX histone (γH2AX), a central protein that contributes to genome stability through the signaling of DNA damage. In conclusion, our results show that chronic exercise modulates redox homeostasis in WAT, improving antioxidant capacity, and mitochondrial function. This hormetic remodeling of adipocyte redox balance points to improved adipocyte health and seems to be directly associated with the beneficial effects of exercise.

Binge eating disorder, frequency of depression, and systemic inflammatory state in individuals with obesity - A cross sectional study.

Introduction: Binge eating disorder (BED) is the most prevalent eating disorder in individuals with obesity. Its association with factors that control hunger and satiety has not yet been elucidated. We evaluated whether levels of inflammatory markers, frequency of psychiatric comorbidities, and appetite-related hormones levels differ between individuals with obesity with and without BED. Subjects and methods: The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-5 - Clinician Version (SCID-5-CV), Binge Eating Scale, and Hospital Anxiety and Depression Scale were evaluated in 39 individuals with obesity. Plasma levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), leptin, ghrelin, and glucagon-like peptide-1 (GLP-1) were measured. Results: Individuals of the BED group exhibited significantly higher percentages of altered eating patterns (hyperphagia, bingeing, post-dinner eating, feeling "stuffed", and emotional eating), higher depressive symptom scores and levels of leptin, CRP, and TNF-α, compared to those from the non-BED group. Logistic regression showed that BED was independently associated with depressive symptoms and CRP levels. Conclusion: Individuals with obesity and BED showed greater psychiatric comorbidity, worse eating patterns and worse inflammatory profile than those without BED. BED should be assessed as an indicator of clinical severity in patients with obesity.

Connexin Expression in Pituitary Adenomas and the Effects of Overexpression of Connexin 43 in Pituitary Tumor Cell Lines.

Gap junction intercellular communication (GJIC) is considered a key mechanism in the regulation of tissue homeostasis. GJIC structures are organized in two transmembrane channels, with each channel formed by connexins (Cxs). GJIC and Cxs expression alterations are related to the process of tumorigenesis in different cell types. Pituitary neuroendocrine tumors (PitNETs) represent 15-20% of intracranial neoplasms, and usually display benign behavior. Nevertheless, some may have aggressive behavior, invading adjacent tissues, and featuring a high proliferation rate. We aimed to assess the expression and relevance of GJIC and Cxs proteins in PitNETs. We evaluated the mRNA expression levels of Cx26, 32, and 43, and the protein expression of Cx43 in a series of PitNETs. In addition, we overexpressed Cx43 in pituitary tumor cell lines. At the mRNA level, we observed variable expression of all the connexins in the tumor samples. Cx43 protein expression was absent in most of the pituitary tumor samples that were studied. Moreover, in vitro studies revealed that the overexpression of Cx43 decreases cell growth and induces apoptosis in pituitary tumor cell lines. Our results indicate that the downregulation of Cx43 protein might be involved in the tumorigenesis of most pituitary adenomas and have a potential therapeutic value for pituitary tumor therapy.

Serum and Urinary Neutrophil Gelatinase-Associated Lipocalin Are Not Associated With Serum Redox Parameters in Amateur Athletes After an Ultramarathon.

Objective: To evaluate the relationship between oxidative stress and NGAL levels in blood and urine of amateur athletes after participating in a 100 km ultramarathon. Methodology: The sample was composed of seven athletes, submitted to anthropometric assessment, cardiopulmonary exercise test, collection of urine and blood, measurement of body weight. The rate of perceived exertion (RPE), competition duration, heart rate (HR), energy expenditure and oxygen consumption (V'O2") were also measured during the event. The energy consumption during the race was verified at its end. The analyses were based on the means (M) and respective standard deviations (SD), with statistical significance set at 5% (p < 0.05). Paired t-test was used for comparison between the periods before and after the competition, and Pearson's correlation coefficient was used to measure the linear correlation between quantitative variables. Results: Body mass index (BMI) of the sample was 25.75 kg/m2 ± 3.20, body fat percentage 18.54% ± 4.35% and V'O2"max 48.87% ± 4.78. Glucose, cortisol, and neutrophil gelatinase-associated lipocalin (NGAL) (p < 0.01) as well as glutathione peroxidase (GPx) active were higher after the race when compared to basal values. Moreover, lactate, creatinine, microalbuminuria, and glomerular filtration rate (GFR) (p < 0.001) were also higher after the race. After the competition, there was a significant correlation only between serum NGAL and creatinine, which was classified as strong and positive (r: 0.77; p < 0.05). There was a significant reduction (p < 0.05) of body weight after the event (72.40 kg ± 9.78) compared to before it (73.98 kg ± 10.25). In addition, we found an increase of RPE (p < 0.001) after the race. The competition lasted 820.60 min (±117.00), with a 127.85 bpm (±12.02) HR, a 2209.72 kcal ± 951.97 energy consumption, 7837.16 kcal ± 195.71 energy expenditure, and 28.78 ml/kg/min-1 (±4.66) relative V'O2"max. Conclusion: The lack of correlation between oxidative stress biomarkers and serum and urine NGAL suggests that NGAL is more sensitive to inflammatory processes than to ROS levels.

Subacute and low-dose tributyltin exposure disturbs the mammalian hypothalamus-pituitary-thyroid axis in a sex-dependent manner.

Tributyltin (TBT) is an endocrine disruptor chemical (EDC) capable of altering the proper function of the hypothalamus-pituitary thyroid (HPT) axis. This study aimed to evaluate the subacute effects of TBT on the HPT axis of male and female rats. A dose of 100 ng/kg/day TBT was used in both sexes over a 15-day period, and the morphophysiology and gene expression of the HPT axis were assessed. TBT exposure increased the body weight in both sexes, while food efficiency increased - only in male rats. It was also possible to note alterations in the thyroid, with the presence of a stratified epithelium, cystic degeneration, and increased interstitial collagen deposition. A reduction in T3 and T4 levels was only observed in TBT male rats. A reduction in TSH levels was observed in TBT female rats. Evaluating mRNA expression, we observed a decrease in hepatic D1 and TRH mRNA levels in TBT female rats. An increase in D2 mRNA expression in the hypothalamus was observed in TBT male rats. Additionally, no significant changes in TRH or hepatic D1 mRNA expression in TBT male rats or in hypothalamic D1 and D2 mRNA expression in TBT female rats were observed. Thus, we can conclude that TBT has different toxicological effects on male and female rats by altering thyroid gland morphophysiology, leading to abnormal HPT axis function, and even at subacute and low doses, it may be involved in complex endocrine and metabolic disorders.

Coupling of GABA Metabolism to Mitochondrial Glucose Phosphorylation.

Glucose and oxygen (O2) are vital to the brain. Glucose metabolism and mitochondria play a pivotal role in this process, culminating in the increase of reactive O2 species. Hexokinase (HK) is a key enzyme on glucose metabolism and is coupled to the brain mitochondrial redox modulation by recycling ADP for oxidative phosphorylation (OXPHOS). GABA shunt is an alternative pathway to GABA metabolism that increases succinate levels, a Krebs cycle intermediate. Although glucose and GABA metabolisms are intrinsically connected, their interplay coordinating mitochondrial function is poorly understood. Here, we hypothesize that the HK and the GABA shunt interact to control mitochondrial metabolism differently in the cortex and the hypothalamus. The GABA shunt stimulated mitochondrial O2 consumption and H2O2 production higher in hypothalamic synaptosomes (HSy) than cortical synaptosomes (CSy). The GABA shunt increased the HK coupled to OXPHOS activity in both population of synaptosomes, but the rate of activation was higher in HSy than CSy. Significantly, malonate and vigabatrin blocked the effects of the GABA shunt in the HK activity coupled to OXPHOS. It indicates that the glucose phosphorylation is linked to GABA and Krebs cycle reactions. Together, these data shed light on the HK and SDH role on the metabolism of each region fed by GABA turnover, which depends on the neurons' metabolic route.

COVID-19 and thyroid function: What do we know so far?

Coronavirus disease 2019 (COVID-19) was characterized as a pandemic in March, 2020 by the World Health Organization. COVID-19 is a respiratory syndrome that can progress to acute respiratory distress syndrome, multiorgan dysfunction, and eventually death. Despite being considered a respiratory disease, it is known that other organs and systems can be affected in COVID-19, including the thyroid gland. Thyroid gland, as well as hypothalamus and pituitary, which regulate the functioning of most endocrine glands, express angiotensin-converting enzyme 2 (ACE2), the main protein that functions as a receptor to which SARS-CoV-2 binds to enter host cells. In addition, thyroid gland is extremely sensitive to changes in body homeostasis and metabolism. Immune system cells are targets for thyroid hormones and T3 and T4 modulate specific immune responses, including cell-mediated immunity, natural killer cell activity, the antiviral action of interferon (IFN) and proliferation of T- and B-lymphocytes. However, studies show that patients with controlled hypothyroidism and hyperthyroidism do not have a higher prevalence of COVID-19, nor do they have a worse prognosis when infected with the virus. On the other hand, retrospective observational studies, prospective studies, and case reports published in the last two years reported abnormal thyroid function related to acute SARS-CoV-2 infection or even several weeks after its resolution. Indeed, a variety of thyroid disorders have been documented in COVID-19 patients, including non-thyroidal illness syndrome (NTIS), subacute thyroiditis and thyrotoxicosis. In addition, thyroid disease has already been reported as a consequence of the administration of vaccines against SARS-CoV-2. Overall, the data revealed that abnormal thyroid function may occur during and in the convalescence post-COVID condition phase. Although the cellular and molecular mechanisms are not completely understood, the evidence suggests that the "cytokine storm" is an important mediator in this context. Thus, future studies are needed to better investigate the pathophysiology of thyroid dysfunction induced by COVID-19 at both molecular and clinical levels.

Cryopreserved Rat Thyroid Autotransplantation in the Treatment of Postoperative Hypothyroidism.

To verify the viability and functionality of cryopreserved thyroid autotransplantation in rats who underwent total thyroidectomy in the treatment of postoperative hypothyroidism. Thirty-two Wistar rats were randomly assigned into groups (G) with eight animals each: control (CG); simulation (SG); hypothyroidism (HTG) and transplanted (TG). At the beginning and in the 13th week of the experiment, serum levels of total T3, free T4, TSH and calcium were determined. In both the first and 14th weeks, scintigraphic examinations, 99m-Tc pertechnetate radioisotope biodistribution and histopathology were performed. In the 14th week, the expression of proliferating cell nuclear antigen (PCNA) and cellular apoptosis (caspase-3) were also evaluated. In the 13th week, the transplanted animals had normal serum levels of total T3 and free T4. TSH levels showed a tendency towards normality. In the 14th week, scintigraphic exams displayed graft isotopic uptake in all animals in the TG group. Histological examinations 13 weeks after transplantation showed the viability and functionality of thyroid follicles. PCNA revealed significant immunoreactivity of the graft (p < 0.001) when the TG was compared to the CG. There was no difference between CG and TG considering the expression of activated caspase-3. The experimental study confirmed the viability and functionality of thyroid autotransplantation implanted in skeletal muscle with evidence of cell proliferation without cellular apoptosis. This surgical strategy was effective in the treatment of postoperative hypothyroidism.

In vitro antitumoral effects of the steroid ouabain on human thyroid papillary carcinoma cell lines.

Ouabain is a steroid described as a compound extracted from plants that is capable of binding to Na+ , K+ -ATPase, inhibiting ion transport and triggering cell signaling pathways. Due to its positive ionotropic effect, ouabain was used for more than 200 years for the treatment of cardiac dysfunctions. Numerous antitumor effects of ouabain have been described so far; however, its role on thyroid cancer is still poorly understood. Therefore, the aim of the present work was to evaluate the effect of ouabain on the biology of human papillary thyroid cancer cells. For this, three human thyroid cell lines were used: NTHY-ori, a non-tumor lineage, BCPAP and TPC-1, both derived from papillary carcinomas. Cells were cultured in the presence or absence of ouabain. Subsequently, we evaluated its effects on the viability, cell death, cell cycle, and migratory ability of these cell lines. We also investigated the impact of ouabain in IL-6/IL-6R and epithelial to mesenchymal transition markers expression. Our results indicate that ouabain (10-7 M), decreased the number of NTHY-ori, TPC-1 and BCPAP viable cells and induced cell cycle arrest after in vitro culture, but did not appear to promote cell death. In TPC-1 cells ouabain also inhibited cell migration; increased IL-6/IL-6R expression and IL-6 secretion; and diminished vimentin and SNAIL-1 expression. Collectively, our results indicate that ouabain has an antitumoral role on human papillary thyroid carcinomas in vitro. Even though additional studies are necessary, our work contributes to the discussion of the possibility of new clinical trials of ouabain.

Bariatric Embolization in the Treatment of Patients with a Body Mass Index Between 30 and 39.9 kg/m2 (Obesity Class I and II) and Metabolic Syndrome, a Pilot Study.

INTRODUCTION: To evaluate the efficacy and clinical safety of bariatric arterial embolization (BAE) in adults with body mass index (BMI) between 30 and 39.9 kg/m2 and metabolic syndrome (MS). MATERIALS AND METHODS: Between March and August 2018, ten female participants between 21 and 48-years-old, median BMI of 36.37 ± 2.58 kg/m2 and MS were enrolled in this prospective trial. We embolized the fundal branches from the left gastric and other artery sources, which resulted in embolization of at least two arteries in 9 out 10 participants. Six months after bariatric embolization, efficacy was assessed by changes in total body weight (TBW), ghrelin and Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) levels and by changes in quality of life (QOL) and in binge eating scale (BES) scores. Safety was assessed by the identification of any related complications, including gastric ulcers, screened by gastrointestinal endoscopy, performed before and one week and one month after BAE. RESULTS: Six months after embolization, TBW decreased by 6.8% (6.22 kg ± 3.6;p = .01), serum ghrelin dropped from 25.39 pg/ml ± 10.63 to 17.1 ± 8.07 (p = 0.01), and HOMA-IR decreased from 7.29 ± 5.66 to 3.73 ± 1.99 (p = 0.01). The QOL scores improved from 59.64 ± 5.59 to 69.02 ± 11.97 (p < 0.05) and in the BES from 21.50 ± 8.89 to 9.60 ± 4.40 (p = 0.01). Endoscopy revealed symptomatic gastric ulcers in two participants, which had healed without sequelae. In one participant, ultrasound revealed an asymptomatic focal arterial thrombus at the left distal radial artery puncture site. CONCLUSION: BAE is effective in reducing weight, insulin resistance and ghrelin levels and improving BES and QOL scores in patients with class I and II obesity and MS, with no major complications.

Combining the American Thyroid Association's Ultrasound Classification with Cytological Subcategorization Improves the Assessment of Malignancy Risk in Indeterminate Thyroid Nodules.

Background: The risk of malignancy (RoM) of indeterminate thyroid nodules (ITNs) shows a high variability in interinstitutional cohorts. The RoM is partially associated with the cytological degree of atypia and the ultrasound (US) pattern. This study evaluated the cancer risk of ITNs by jointly considering the cytological subcategory and the American Thyroid Association (ATA)-based US risk classification. Methods: This study features a retrospective cohort from two Brazilian centers comprising 238 ITNs with confirmed outcomes. US classification, according to ATA-based guidelines, and cytological subcategorization were determined. The cytological subgroups were as follows: (1) nuclear atypia (NA) related to papillary thyroid carcinoma (PTC) but insufficient to categorize the cytology as suspicious for malignancy; (2) architectural atypia without NA (AA); (3) both architectural and nuclear atypia (ANA); (4) oncocytic pattern (OP) without NA; and (5) NA not related to PTC (NANP). NA was divided into three subgroups: nuclear size and shape, nuclear membrane appearance, and/or chromatin aspects. Results: The overall frequency of malignancy was 39.5%. Among the cytological subcategories, the highest RoM was related to the NA (43.9%) and to the ANA (43.5%), followed by AA (29.4%), and OP (9.4%). NA was positively and independently associated with cancer (odds ratio [OR]: 4.5; confidence interval [CI: 1.2-16.6]) as was the occurrence of ANA (OR 6.6 [CI 1.5-29.5]). AA and OP were not independently associated with cancer. Both ATA-based high- and intermediate-risk categories showed an independent association with cancer (OR 6.8 [CI 2.9-15.5] and OR: 2.6 [CI 1.1-5.8], respectively). ITNs with cytological findings of NA or ANA when combined with intermediate US patterns had RoM values of 47.5% and 56.7%, respectively. Both cytological subcategories, when combined with the ATA high-suspicion class reached an RoM >70%. The type of NA with the highest odds for cancer was related to the nuclear membrane (OR 11.5). Conclusions: The RoM of ITNs can reach almost 80% when both NA and ATA-based high-risk US features are present. The presence of such cytological features also increased the RoM in the ATA-based intermediate-risk US category. In addition, AA and OP were not independently related to higher cancer risk. These results strengthen the recommendations for combing cytological subcategorization and US risk classification in the workup for ITNs before the decision of a molecular testing, clinical observation, or diagnostic surgery.

Subacute exposure to lead promotes disruption in the thyroid gland function in male and female rats.

Exposure to heavy metals, such as lead, is a global public health problem. Lead has a long historic relation to several adverse health conditions and was recently classified as an endocrine disruptor. The aim of this study was to investigate the effects of subacute exposure to lead on the thyroid gland function. Adult male and female Wistar rats received a lead acetate solution containing 10 or 25 mg/kg, by gavage, three times a week, for 14 days. One week later, behavioral testing showed no alterations in anxiety and motor-exploratory parameters, as evaluated by Open-Field and Plus-Maze Tests, but impairment in learning and memory was found in the male 25 mg/kg lead-treated group and in both female lead-treated groups, as evaluated by the Inhibitory Avoidance Test. After one week, serum levels of tT3 were reduced in the 25 mg/kg female group and in the 10 mg∕ kg male group. However, tT4 levels were increased in the 25 mg/kg male group and in both female treated groups. TSH levels did not change and lead serum levels were undetectable. Morphologic alterations were observed in the thyroid gland, including abnormal thyroid parenchyma follicles of different sizes, epithelial stratification and vacuolization of follicular cells, decrease in colloid eosinophilia and vascular congestion, accompanied by morphometric alterations. An increase in collagen deposition was also observed. No differences were observed in TPO activity or protein expression, H2O2 generation by NADPH oxidases or hepatic D1 mRNA expression. However, thyroid NIS protein expression was considerably decreased in the male and female lead-treated groups, while TSHr expression was decreased in the 25 mg/kg female lead-treated group. These findings demonstrated that subacute exposure to lead acetate disrupts thyroid gland function in both sexes, leading to morphophysiological impairment and to changes in learning and memory abilities.

High-dose Nandrolone Decanoate induces oxidative stress and inflammation in retroperitoneal adipose tissue of male rats.

The non-therapeutic use of the androgenic anabolic steroid Nandrolone Decanoate is popular due to its effects on physical performance and body composition, especially for its lipolytic and anabolic effects associated. However, high doses of such drugs are often associated with a series of pathologies related to unbalanced redox homeostasis, which, in turn, can be linked to inflammation. The oxidative stress onset could deregulate the secretion of cytokines, evidencing a dysfunctional adipocyte. Thus, the aim of this study was to investigate the effect of supraphysiological doses of Nandrolone Decanoate on redox homeostasis of retroperitoneal fatpad of male rats and its relationship with cytokines-based inflammatory signaling. Hydrogen peroxide production was assessed in the retroperitoneal fat pad of adult male rats which received either 10 mg kg of Nandrolone Decanoate or only a vehicle. Also, catalase, superoxide dismutase and glutathione peroxidase activities were measured, together with total reduced thiols and protein carbonylation, as well as IL-1ß, TNF-α, and IL-6 local levels. High doses of Nandrolone Decanoate caused an increase in the hydrogen peroxide production, together with lower activities of the antioxidant enzymes and lower levels of total reduced thiol. There were also higher protein carbonylation and greater levels of IL-1ß, TNF-α, and IL-6 in the treated group compared to control group. Therefore, it was possible to verify that high doses of Nandrolone Decanoate cause oxidative stress and induce higher inflammatory signaling in retroperitoneal fat pad of male rats.

Hypoglycaemic effect of resveratrol in streptozotocin-induced diabetic rats is impaired when supplemented in association with leucine.

Studies have shown synergistic and independent effects of leucine and resveratrol (RSV) as possible therapeutic agents to ameliorate metabolic disorders. Thus, the objective of this study was to investigate the effects of supplementation with leucine and RSV, alone and in combination, on metabolic changes in white adipose tissue of neonatally STZ-induced diabetic rats. After weaning, the rats were treated with trans-resveratrol (0.6 mg/kg/dose) and/or leucine (1.35 mg/kg/dose) administered orally. The animals were euthanized at age 16 weeks for blood analyses. Subcutaneous (SC), periepididymal (PE) and retroperitoneal (RP) fat pads were weighed. Adipocytes from PE and RP pads were isolated for morphometric analysis. Long-term supplementation with RSV promoted adiposity recovery, prevented hypoinsulinemia and improved the metabolic profile of the diabetic rats. However, some of these effects were impaired when RSV was associated with leucine. The diabetic rats supplemented with leucine alone showed no significant improvement in metabolic disorders.

The Gut Microbiome and Metabolome of Two Riparian Communities in the Amazon.

During the last decades it has become increasingly clear that the microbes that live on and in humans are critical for health. The communities they form, termed microbiomes, are involved in fundamental processes such as the maturation and constant regulation of the immune system. Additionally, they constitute a strong defense barrier to invading pathogens, and are also intricately linked to nutrition. The parameters that affect the establishment and maintenance of these microbial communities are diverse, and include the genetic background, mode of birth, nutrition, hygiene, and host lifestyle in general. Here, we describe the characterization of the gut microbiome of individuals living in the Amazon, and the comparison of these microbial communities to those found in individuals from an urban, industrialized setting. Our results showed striking differences in microbial communities from these two types of populations. Additionally, we used high-throughput metabolomics to study the chemical ecology of the gut environment and found significant metabolic changes between the two populations. Although we cannot point out a single cause for the microbial and metabolic changes observed between Amazonian and urban individuals, they are likely to include dietary differences as well as diverse patterns of environmental exposure. To our knowledge, this is the first description of gut microbial and metabolic profiles in Amazonian populations, and it provides a starting point for thorough characterizations of the impact of individual environmental conditions on the human microbiome and metabolome.

Effects of Metformin on TSH Levels and Benign Nodular Goiter Volume in Patients Without Insulin Resistance or Iodine Insufficiency.

Objectives: To evaluate the impact of metformin (MTF) use on TSH levels, thyroid volume and volume of benign thyroid nodules (TNs). Additionally, to study if iodine status influences the outcomes. Methods: A total of 23 euthyroid patients (42 TNs) with benign thyroid nodules, diagnosed by fine needle aspiration biopsy, were randomly assigned to MTF or placebo (P) use for 6 months. Serum TSH, homeostatic model assessment for insulin resistance (HOMA-IR), and urinary iodine concentrations (UIC) were assessed. Ultrasound was used to evaluate TNs and thyroid volumes (TV) and their variations throughout the study. Diabetic patients, those undergoing levothyroxine replacement, and/or using thyroid- or insulin level-influencing drugs were excluded. Results: The sample consisted predominantly of patients without IR. Both intervention groups were similar regarding several confounding variables and showed a comparable median UIC. Serum TSH decreased significantly after MTF (-0.21 vs. 0.09 mUI/L in the P group; p = 0.015). At 6 months, no significant variations were found between groups with respect to TN volumes, TV, HOMA-IR, or body mass index (BMI). However, a tendency toward enlargement of TV with placebo (16.0%; p = 0.09) and a protective effect of MTF on growing TN (OR: 0.25; CI 0.05-1.20) was detected after excluding patients with IR (a lower UIC subgroup). The reduction on TSH levels with MTF maintained in the population without iodine insufficiency (-0.24 vs. +0.07 in the P group; p = 0.046) and was accentuated in those with excessive or more than adequate UIC (-0.69; p = 0.043). A protective effect of MTF on growing TN was suggested (OR: 0.11; IC: 0.02-0.84) in those with higher UIC. Conclusions: This study demonstrated that MTF caused a reduction in TSH levels in benign nodular goiter. This effect was more accentuated in patients with higher levels of UIC and was accompanied by a suggested protective effect on TN enlargement.

Impact of violacein from Chromobacterium violaceum on the mammalian gut microbiome.

Violacein is a violet pigment produced by Chromobacterium violaceum that possesses several functions such as antibacterial, antiviral, antifungal, and antioxidant activities. The search for potential compounds and therapies that may interfere with and modulate the gut microbial consortia without causing severe damage and increased resistance is important for the treatment of inflammatory, allergic, and metabolic diseases. The aim of the present work was to evaluate the ability of violacein to change microbial patterns in the mammalian gut by favoring certain groups over the others in order to be used as a therapy for diseases associated with changes in the intestinal microflora. To do this, we used male Wistar rats, and administered violacein orally, in low (50 µg/ml) and high (500 µg/ml) doses for a month. Initially, the changes in the microbial diversity were observed by DGGE analyses that showed that the violacein significantly affects the gut microbiota of the rats. Pyrosequencing of 16S rDNA was then employed using a 454 GS Titanium platform, and the results demonstrated that higher taxonomic richness was observed with the low violacein treatment group, followed by the control group and high violacein treatment group. Modulation of the microbiota at the class level was observed in the low violacein dose, where Bacilli and Clostridia (Firmicutes) were found as dominant. For the high violacein dose, Bacilli followed by Clostridia and Actinobacteria were present as the major components. Further analyses are crucial for a better understanding of how violacein affects the gut microbiome and whether this change would be beneficial to the host, providing a framework for the development of alternative treatment strategies for intestinal diseases using this compound.